Understanding the Pathophysiology of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a severe, X-linked neuromuscular disorder caused by mutations in the dystrophin gene, leading to absence of functional dystrophin protein. Dystrophin plays a critical role in maintaining the structural integrity of muscle fibers by linking the intracellular cytoskeleton to the extracellular matrix. Its loss renders muscle cells highly susceptible to damage during normal contraction. Repeated cycles of muscle injury and inadequate repair result in chronic inflammation, progressive muscle fiber degeneration, and replacement of muscle tissue with fat and fibrotic tissue. Over time, this process leads to worsening skeletal muscle weakness as well as cardiomyopathy and respiratory failure. Current understanding of DMD pathophysiology highlights the interplay between mechanical instability, inflammatory signaling, impaired regeneration, and secondary downstream pathways, providing important insights that are shaping the development of targeted and disease-modifying therapies.